After a second complete spinal cord severing, lampreys can recover and regenerate just as impressively as they do after the first, according to a new study.

The study opens up a new path for identifying pro-regenerative molecules and potential therapeutic targets for human spinal cord injury.

Spontaneous recovery from spinal cord injury is almost unheard of in humans and other mammals, but many vertebrates fare better. The eel-like lamprey, for instance, can fully regenerate its spinal cord even after being severed—within three months the lamprey is swimming, burrowing, and flipping around again, as if nothing had happened.

“We’ve determined that central nervous system regeneration in lampreys is resilient and robust after multiple injuries. The regeneration is nearly identical to the first time, both anatomically and functionally,” says senior author Jennifer Morgan, director of the University of Chicago-affiliated Marine Biological Laboratory’s Eugene Bell Center for Regenerative Biology and Tissue Engineering.

Morgan’s lab has been focusing on the descending neurons, which originate in the brain and send motor signals down to the spinal cord. Some of these descending neurons regenerate after central nervous system injury in lamprey, while others die.

“We are beginning to isolate individual descending neurons and look at their transcriptional profiles (gene activity) to see if we can determine what makes some of them better at regenerating than others,” Morgan says.

“The ‘good’ regenerators, for example, may express molecules that are known to promote growth during development. That’s one hypothesis,” she says.

Observing how the descending neurons respond to a second injury can help the team tease out the factors required for repeated, resilient regeneration, which could have implications for designing better strategies for treatments aimed at promoting central nervous system regrowth after injury or disease.